| Eligibility |
Inclusion Criteria:
1. Be between 18-75 years old;
2. Sign written informed consent, and be able to comply with the visits and related
procedures stipulated in the plan;
3. Histopathological diagnosis was extrahepatic cholangiocarcinoma, including hilar
cholangiocarcinoma and distal cholangiocarcinoma, and had undergone radical resection;
4. The pathology report of the patient must confirm complete resection (recovery from the
operation to be disease-free, and the sample has negative margins R0, R1);
5. The patient must be treated within 12 weeks after the radical resection;
6. No anti-tumor treatment before radical resection, including radiotherapy and
chemotherapy, targeted therapy and immunotherapy;
7. ECOG score 0-1 points;
8. Expected survival time> 6 months;
9. With sufficient organ and bone marrow function, the laboratory test values within 7
days before randomization meet the following requirements (no blood components, cell
growth factors, albumin and other corrective treatment drugs are allowed to meet the
conditions), as follows :1) Blood routine: absolute neutrophil count (ANC) =1.5×109/L;
platelet count (platelet, PLT) =75×10 9/L; hemoglobin content (hemoglobin, HGB) =9.0 g
/dL;2) Liver function: serum total bilirubin (TBIL) = 2×upper limit of normal value
(ULN); alanine aminotransferase (ALT) and aspartate amino transfer Enzyme (aspartate
transferase, AST) =5×ULN; serum albumin =28 g/L; alkaline phosphatase (alkaline
phosphatase, ALP) =5×ULN;3) Renal function: serum creatinine (Cr) = 1.5×ULN or
creatinine clearance (clearance of creatinine, CCr) = 50 mL/min (Cockcroft-Gault
formula); urine routine results show urine protein <2+; against baseline For patients
whose urine protein is =2+ by routine urine test, 24-hour urine collection and 24-hour
urine protein quantitative <1g should be performed;4) Coagulation function:
International normalized ratio (INR) and activated partial thromboplastin time (APTT)
= 1.5 times ULN.
10. Female patients of childbearing age or male patients whose sexual partners are females
of childbearing age should take effective contraceptive measures throughout the
treatment period and 6 months after the last treatment.
Exclusion Criteria:
1. Diagnosis of other malignant diseases outside the biliary tract within 5 years before
the first administration (excluding radically cured skin basal cell carcinoma, skin
squamous cell carcinoma, and/or radically excised carcinoma in situ);
2. Currently participating in interventional clinical research treatment, or received
other research drugs or used research devices within 4 weeks before the first
administration;
3. Have received the following therapies in the past: anti-PD-1, anti-PD-L1 or anti-PD-L2
drugs or for another stimulating or synergistic inhibition of T cell receptors (for
example, CTLA-4, OX-40, CD137) drug;
4. Have received radiotherapy for biliary tract tumors in the past;
5. Received Chinese patent medicines with anti-tumor indications or immunomodulatory
drugs (including thymosin, interferon, interleukin, except for local use to control
pleural effusion) systemic systemic treatment within 2 weeks before the first
administration;
6. An active autoimmune disease that requires systemic treatment (such as the use of
disease-relieving drugs, glucocorticoids, or immunosuppressive agents) occurred within
2 years before the first administration. Alternative therapies (such as thyroxine,
insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) are
not considered systemic treatments. Known history of primary immunodeficiency. Only
patients with positive autoimmune antibodies need to confirm whether there are
autoimmune diseases based on the judgment of the investigator;
7. Are receiving systemic glucocorticoid therapy (excluding nasal spray, inhaled or other
local glucocorticoids) or any other form of immunosuppressive therapy within 4 weeks
before the first administration of the study. Note: Physiological doses of
glucocorticoids are allowed (=10 mg/day prednisone or equivalent drugs);
8. There is clinically uncontrollable pleural effusion/abdominal effusion (patients who
do not need to drain the effusion or stop drainage for 3 days without a significant
increase in effusion can be included in the group)
9. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic
hematopoietic stem cell transplantation
10. Those who are known to be allergic to the active ingredients or excipients of
Sintilimab
11. Before starting treatment, have not fully recovered from toxicity and/or complications
caused by any intervention (ie, = Grade 1 or reached baseline, excluding fatigue or
hair loss)
12. Known history of human immunodeficiency virus (HIV) infection (ie HIV 1/2 antibody
positive)
13. Untreated active hepatitis B (defined as HBsAg positive and the number of copies of
HBV-DNA detected at the same time is greater than the upper limit of normal value of
the laboratory department of the research center).Note: Hepatitis B subjects who meet
the following criteria can also be included in the group:1) The HBV viral load before
the first administration is less than 2.5×103 copies/ml (500 IU/ml), and the subject
should receive anti-HBV treatment during the entire study treatment period;2) For
subjects with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), there is
no need to receive preventive anti-HBV treatment, but close monitoring of virus
reactivation is required.
14. Active HCV infected subjects (HCV antibody-positive and HCV-RNA level is higher than
the lower limit of detection);
15. Have received a live attenuated vaccine within 4 weeks before the first dose;
16. Pregnant or lactating women;
17. There are any serious or uncontrollable systemic diseases, such as:1) The resting
electrocardiogram has major abnormalities in rhythm, conduction, or morphology that
are severe and difficult to control, such as complete left bundle branch block, heart
block above ? degree, ventricular arrhythmia or atrial fibrillation;2) Unstable angina
pectoris, congestive heart failure, chronic heart failure of New York Heart
Association (NYHA) grade = 2;3) Any arterial thrombosis, embolism or ischemia, such as
myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic
attack, occurred within 6 months before being selected for treatment;4) Major surgery
(craniotomy, thoracotomy or laparotomy) or unhealed wounds, ulcers or fractures have
been received within 4 weeks before the first administration. Have received tissue
biopsy or other minor surgical procedures within 7 days before the first
administration, except for venipuncture catheters for the purpose of intravenous
infusion;5) Unsatisfactory blood pressure control (systolic blood pressure>140 mmHg,
diastolic blood pressure>90 mmHg);6) Active tuberculosis;7) There is an active or
uncontrolled infection that requires systemic treatment;8) There is clinically active
diverticulitis, abdominal abscess, gastrointestinal obstruction;9) Liver diseases such
as cirrhosis, decompensated liver disease, acute or chronic active hepatitis;10) Poor
control of diabetes (fasting blood glucose (FBG)> 10mmol/L);11) Urine routine test
shows urine protein =++, and the 24-hour urine protein quantitative is confirmed to be
>1.0 g;12) Patients with mental disorders who cannot cooperate with treatment;
18. The medical history or disease evidence, abnormal treatment or laboratory test values
that may interfere with the test results, prevent the subject from participating in
the study, or the investigator believes that it is not suitable for inclusion in the
group. The investigator believes that there are other potential risks and is not
suitable for participation.
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